Evaluation of reference intervals for immunoglobulins in children using indirect methods

This study aimed to determine reference intervals for immunoglobulin G (IgG), IgA, IgM, and IgE concentrations in the pediatric population using an immunonephelometric method. The reliability of the derived reference intervals was assessed by comparing them with results from the Canadial Laboratory Initiative on Pediatric Reference Intervals (CALIPER) study, which employed direct methods.

A total of 120 194 IgG, IgA, IgM, and IgE results from 2020 to 2023 were extracted from the hospital database. After applying the necessary exclusion criteria, 2 groups were formed: 1 with exclusions (n = 70 565) and 1 without (n = 69 435). Immunoglobulin results were partitioned by age and sex, where required, using the Harris-Boyd method. Reference intervals were calculated using the refineR and Kolmogorov-Smirnov Distance (kosmic) indirect reference interval calculation algorithms, with and without outlier exclusion, to assess the impact of outliers.

A statistically significant difference between sexes was observed only for the IgM concentrations-specifically, in the age group of 1 month to 1 year. In both groups, with and without outlier exclusion, a difference was observed only for the IgE test in the group aged 1 to 18 years, where a higher frequency of pathologic results was observed. The reference intervals calculated using the kosmic and refineR algorithms were generally consistent with each other; however, substantial differences were observed for IgA in the group aged 2 to 3 years and for the IgE test. The patterns observed in the reference intervals were consistent with those reported in the CALIPER study.

This study successfully verified the CALIPER pediatric reference intervals for IgG, IgA, IgM, and IgE concentrations using the immunonephelometric method.